This proposal requests support for a Keystone Symposia meeting entitled Protein-RNA Interactions in Biology and Disease, organized by Thomas Tuschl, Mikiko C. Siomi and Gideon Dreyfuss, which will be held in Santa Fe, New Mexico from March 4 - 9, 2012. There is increasing recognition regarding the role of RNA-binding proteins in neurodevelopmental and neurodegenerative diseases. Cellular functions depend on numerous protein-coding and noncoding RNAs and the RNA-binding proteins (RBPs) associated with them, which form ribonucleoprotein complexes (RNPs). Mutations that disrupt either the RNA or protein components of RNPs or the factors required for their assembly can be deleterious. For example, research implicates dysfunctional RNA-binding proteins in diseases such as amyotrophic lateral sclerosis, frontotemporal lobar degeneration, Fragile X Sydrome, Huntington's Disease, paraneoplastic neurologic degeneration, and spinal muscular atropy among others. The discovery of disease-causing mutations in RNAs or their interacting RBPs not only adds to our growing understanding of RNA biology and chemistry, but also offers new therapeutic targets and contributes to ongoing efforts developing mRNA-targeting antisense and RNAi therapeutics. This meeting focuses on a general understanding of posttranscriptional gene regulation and how perturbation of complex networks of RNA-protein and RNA-RNP interactions triggers disease. PUBLIC HEALTH RELEVANCE: Posttranscriptional regulation (PTR) of RNA in cells - a rapidly growing research area -plays essential roles in cellular and developmental processes by controlling how RNA is processed in the cell, its stability and transport within the cell, and the translation of RNA into proteins. The Keystone Symposia meeting on Protein- RNA Interactions in Biology and Disease aims to bring together basic researchers studying the molecular details of PTR, including RNA silencing, with pathologists and clinicians interested in understanding how PTR contributes to normal health and disease.